Genetic basis of event-related potentials and their relationship to alcoholism and alcohol use.
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In a series of event-related potential (ERP) studies, we have consistently demonstrated an ERP component correlate of visual short-term memory. There have been frequent reports on the deficits of information encoding, retention, and retrieval in chronic alcoholics. In the present study, we investigated that the ERP mnemonic effects could be influenced by long-term alcohol abuse. ERP data were recorded from 48 controls and 77 alcoholics while the subjects performed a modified delayed matching to sample paradigm using a series of object pictures as stimuli. The alcoholics completed the task with more errors and longer response times than the controls. The major differences in the evoked potentials between the two groups are found at the temporo-occipital and frontal regions in the sample and nonmatching trials, and mostly prominent in the right hemisphere. The current study indicates that the ERP technique can be a useful tool to index short-term memory. The ERP mnemonic effect difference between the two groups may be a reflection of a working memory deficit caused by long-term alcohol abuse. Our data also suggest right hemisphere dysfunction in alcoholics, with deficits in information encoding.
P300 recordings were made from males at high risk (HR) for alcoholism and low-risk (LR) controls, participating in a visual go/no go reaction time paradigm. The go (button press) and no go (inhibit response) stimuli were large and small forms of the same letters. The LR group had significantly larger go than no go P300 amplitudes in the central, parietal, and temporal regions; the HR group manifested no response differences in any region. In the LR group compared to the HR group, both go and no go response amplitudes were larger over the entire head; no group differences in latencies were observed in any region. Surface energy magnitudes paralleled P300 amplitudes and were also larger in the LR group during both go and no go trials. Our findings indicate that HR individuals manifest widespread P300 amplitude deficits while performing a simple information-processing paradigm. These deficits, which may reflect genetic influences, preceded the onset of alcoholism and may function as a phenotypic marker for its development.
The correlational association from 19 electrode sites between peak amplitude and latency for the P3(00) event-related brain potential (ERP) for n = 80 homogeneous subjects was assessed using a simple auditory discrimination task. The correlation strength varied systematically across scalp topography in different ways for the various ERP components. For the target stimuli, P3 amplitude and latency were negatively correlated and most tightly coupled over the frontal-central and right medial/lateral recording sites. In contrast, the N1 produced negative correlations that were strongest over the left and right central/lateral locations; P2 demonstrated a positive correlation that was strongest frontally and centrally; N2 demonstrated a positive correlations that was strongest over the central and parietal sites. ERPs from the standard stimuli produced generally similar patterns for the P3 and P2 components, with only weak or no reliable effects observed for the N1 and N2 potentials. Taken together, the findings suggest that analysis of amplitude/latency correlational relationships can provide information about ERP component generation. Theoretical implications are discussed.
Implicit memory is inferred from repetition priming effects in tasks such as word identification, word fragment completion, and perceptual recognition with masking or brief exposures. In this experiment, we explored whether the visual word and object repetition priming effects can be reflected by features of ERP and whether visual word repetition priming differs from visual object repetition priming. We have observed that (1) pre-exposure to recognizable stimuli (both word and object picture) shortened the response time in identifying their repetitions; (2) repetition of unrecognized scrambles of words or object pictures did not show any effects on ERP patterns; (3) ERPs distinguished recognizable from unrecognizable stimuli; and, (4) repetitions of both words and pictures strongly influenced the patterns of ERPs, though the ERPs to word stimuli differed from the ERPs to picture stimuli.
In order to investigate whether visual object priming differs from visual word priming and whether the visual repetition priming in chronic alcoholic patients is impaired, we performed an ERP study on 27 male control and 67 male alcoholic subjects. Sixty-one electrodes were employed to record ERPs that were elicited by random presentations of object pictures, words, and scrambles for both pictures and words. We also used an implicit task that required subjects to identify whether each stimulus was recognizable. The current experiment revealed that (1) the reaction times to both recognizable picture and word stimuli were significantly shortened by the prior exposures of the same stimuli, (2) control subjects reflected visual object and word priming in different ERP components with different topographic patterns, (3) alcoholic subjects manifested visual word priming in the same ERP component as controls, and (4) the differences in ERP components, both in amplitude and topographic distribution, between the two groups occurred mainly in the different stimuli. These data suggest that the visual object and word priming have distinctive neural processes. The visual object priming in alcoholic subjects may be impaired while the visual word priming seemed to be intact.
Slow brain electrical potentials (SPs) were investigated in a visual-spatialmemory task. Two issues were addressed: (1) the nature and topographic distribution of the potentials obtained under such conditions; and (2) the consistency of the SPs when recorded in six identically configured laboratories. Fifteen young male subjects were studied at each laboratory (total n = 90). The paradigm entailed presentations of paired-visual patterns (S1 and S2), to which subjects responded with a choice reaction time response indicating whether or not the two patterns matched. A biphasic contingent negative variation (CNV) was produced which consisted of an early symmetric component with bilateral foci at posterior temporal sites and a subsequent mid-parietal dominant wave later in the retention interval. Although the CNVs from all laboratories were similar in waveform and in topographic distribution, there were significant inter-laboratory differences in amplitude of the slow potential components. The topographic distributions of the components and the possible role of sampling effects are discussed.
The study of working memory often utilizes a delayed matching to sample paradigm (DMS). Typically in the matching condition, the test and sample stimuli are identical, raising the possible confound of retinotopic projections for the matching stimuli in contrast to the non-matching stimuli. In the present study, 65 healthy subjects performed a modified delayed matching to sample task while monitoring their ERP waveforms. The stimuli consisted of 60 different sample stimuli (S1) and 60 different test stimuli (S2). Half of the S2s were complementary to the sample stimuli (Fit), the other half of the S2s were not complementary (Nonfit). After S2, the subjects pressed one of the buttons to indicate whether the test stimulus fits the sample stimulus. Our statistical results indicated that the ERPs to sample stimuli differed from the ERPs to test stimuli from 200 ms poststimulus to the end of the recording epoch. The ERPs to fitting stimuli were significantly different from those to non-fitting stimuli from 200 to 400 ms poststimulus. The ERP patterns in the present study may reflect ERP mnemonic effect for working memory. Our results ruled out the retinotopic confound as a potential mediator variable, and are in agreement with other animal or human neurophysiological studies on memory.
Scalp recordings of the P300 component of the event-related potential were made from a group of medication-free, chronic male alcoholics and a control group, participating in a visual Go/No Go reaction time paradigm. Subjects were presented with large and small forms of the letters T and V. The large forms (Go stimuli) required a button press with either the left or right hand, whereas the small forms (NO Go stimuli) required response inhibition. Recordings were made from 31 electrodes that, for statistical analyses, were grouped into five regions: frontal, central, parietal, occipital, and temporal. The results indicated that, in each of the five regions, both Go and NO Go response amplitudes were larger in the controls than in the alcoholics. No group differences in latency were observed in any region. Surface energy (Wang et al., Brain Topogr. 6:193-202, 1994) magnitudes paralleled P300 amplitudes and in the controls, compared with the alcoholics, were larger during both Go and No Go trials. Our findings suggest that abstinent, chronic alcoholics differ electro-physiologically from control individuals. These differences are manifested as widespread reductions in P300 amplitudes during the performance of a simple information processing paradigm. The reduced amplitudes may reflect a deficiency in an inhibitory mechanism proposed to underlie P300 generation.
The reduction in the amplitude of the auditory P300 in young adult males at high risk for alcoholism has not been as consistently replicated as has been the reduction in the visual P300 amplitude in the same group. The easier nature of the auditory task was thought to be responsible for the inconsistency. We examined the auditory P300 amplitude in a group that has not yet been studied, young adult sons of alcoholics (mean age = 24.9 years, n = 48), and compared them with age and sex-matched controls (mean age = 27.8 years, n = 23). We found the auditory P300 amplitude to be reduced in the high-risk group and this reduction to be the greatest over the posterior centroparietal and occipital areas when individual leads were examined. We further analyzed the data using current source density, a mathematical transformation that circumvents some of the errors inherent in measuring scalp-evoked potentials, and found reduced current source density in the high-risk group in the posterior central and parietal areas. Thus, we found that a simple auditory oddball task was effective in eliciting P300 differences in groups at high and low risk for alcoholism. The clinical significance of the P300 is discussed, as well as the relevance of task difficulty in eliciting auditory P300 differences in young males at high risk for alcoholism.
Recent studies from our laboratory have resulted in the identification of an event-related potential (ERP) correlate of a visual memory process. This memory process is reflected by a reduction in the voltage of the visual memory potential (VMP) to repeated pictures of unfamiliar faces compared to novel pictures of faces. In the current experiment we used unfamiliar and famous faces in an identical repetition priming paradigm, while the subject differentially recognized famous from non-famous faces. Significant differences in response times were obtained between primed and unprimed familiar faces, but not between primed and unprimed unfamiliar faces. The VMP was reduced to primed unfamiliar faces and significantly diminished to primed familiar faces compared to unprimed stimuli. Priming was typically reflected by a reduction of the VMP at the occipito-temporal region, whereas recognition resulted in a diminution of the VMP at both the occipito-temporal region and at the frontal region. These data support the involvement of differential neural systems for priming and recognition of visual stimuli.
A word priming paradigm involving primed, unprimed, and non-word experimental conditions was used to elicit event-related potentials (ERPs) in normal, young adult males in identically equipped electrophysiology laboratories located in 6 different cities in the USA. Analyses of the average amplitude of a specified latency window containing the N400, the N400 peak amplitude, or the latency of the N400 peak amplitude found no differences among laboratory locations. The shape of the N400 ERP wave form was also found to be highly correlated across laboratory sites for each experimental condition. Comparison of the data with analogous word priming paradigms revealed similar patterns for the N400 components and response times in both the primed and unprimed experimental conditions. These findings suggest that the data from all 6 laboratory locations are consistent with each other and are congruous with those found in other N400 studies and will permit pooling of subject data for future research.
In our previous studies, we have demonstrated an ERP correlate of visual memory with a modified delayed matching-to-sample paradigm using a series of nonsense line drawings or faces as stimuli. In this experiment, we employed pictures of objects to determine whether the ERP can reflect the object recognition process and whether visual stimuli with a verbal label would result in a different topographic distribution from past topography obtained with visual stimuli without a verbal label. The results of this study suggest that the amplitude of the ERP component (c247) to repeated (primed) pictures of common objects was significantly decreased as compared to the unrepeated (unprimed) pictures; the latency for the peak of c247 was decreased for the repeated compared to the unrepeated, and the response time was also significantly shorter to the repeated picture stimuli than to the unrepeated; the topographical distribution of c247 was mainly located in the occipitotemporal areas of the brain. However, the source energy density map showed that the topographic involvement of the brain regions to the c247 was different in the matching and nonmatching trials.
The P3(00) event-related potential (ERP) was elicited in 80 normal, right-handed male subjects using a simple visual discrimination task, with electroencephalographic (EEG) activity recorded at 19 electrodes. P3 amplitude was larger over the right than over the left hemisphere electrode sites primarily at anteromedial locations (F3/4, C3/4) for target, novel, and standard stimuli. The N1, P2, and N2 components also demonstrated hemispheric asymmetries. The strongest P3 hemispheric asymmetries for all stimuli were observed at anterior locations, suggesting a frontal right hemisphere localization for initial stimulus processing, although target stimuli produced larger P3 amplitudes at parietal locations that did novel stimuli. The relationships of hemispheric asymmetries to anatomical variables, background EEG activity, and neurocognitive factors are discussed.
An auditory oddball paradigm was used to record the P300 component of the event-related potential (ERP) in a group of medication-free, chronic male alcoholics (n = 51, mean = 32.2) and a control group (n = 25, mean = 27.2). Each subject received a binaurally presented series of high (1600-Hz)- and low (600-Hz)-frequency tones. The designation of the rare tone (0.125 probability) was alternated across subjects. When the subject detected the rare tone, he made a button press as quickly as possible to record his reaction time. Scalp recordings using the entire 10/20 System, as well as interpolated placements, were made from 31 electrodes. For purposes of statistical analyses, five regional electrode groups were created: F (frontal), C (central), P (parietal), O (occipital), and T (temporal). The results of MANOVA indicated that control P300 amplitudes were significantly greater than those of the alcoholics in all five regions, whereas there were no P300 latency differences between groups in any region. Regional response differences between the groups were also compared with measures of surface energy (SE) (Wang et al., 1994). SE is a recently developed, reference-free global field measure that uses the entire scalp potential field and treats potentials at different positions differently. SE was significantly reduced in the alcoholics compared with the controls in both the C (p < 0.0003) and P (p < 0.0006) regions, although there were no differences in its distribution.(ABSTRACT TRUNCATED AT 250 WORDS)
In this paper, we propose new multivariate composite estimators (MCE) to track multiple channel potential waves of individual and grand averages of recorded potentials at the scalp from a number of trials in a group of subjects. The advantages of these estimators over simple averages used in the literature are that they have larger signal to noise ratios (SNR), and that they have taken into account variations and correlations of the recorded potentials at the electrode sites as well as differences among subjects. Multivariate techniques and composite concept are used for deriving the estimators. We also provide an application to human event-related potentials in a memory for faces experiment.
In this paper, we propose three new measures for topographic studies of event related potentials (ERP) called the surface energy (SE), its density (SED) and the distance of surface energy density fields (DSED) based on the entire scalp current density (SCD) field. These measures have a specific physical meaning, are free of the reference electrode and any physical conductive model of the head. They capture not only spatial properties, but also continuous time elements present and smeared in the original scalp potential records. They provide a common base for comparisons of recorded potentials among different time points, subjects, regions on the scalp, or experimental conditions. We also construct a statistical inference based on these new measures, and provide an application to human event-related potentials in a visual short-term memory experiment.
Event-related potentials (ERPs) were recorded from normal subjects for the purpose of evaluating measurement consistency among six laboratories located in different cities within the United States. At each laboratory location 15 male subjects were tested using a simple auditory stimulus discrimination task and identical electrophysiological equipment and recording methods. Assessment of the N1, P2, N2, and P3(00) potentials from both the target and standard stimuli resulted in no reliable differences among laboratories for component amplitudes, latencies, and scalp distributions. Quantitative evaluation of overall waveform and specific component morphology yielded good to excellent agreement across laboratories. The findings suggest that large-scale inter-laboratory human electrophysiological studies are feasible and may prove of value when using ERPs to evaluate cognitive function in humans.